Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Severe Sickle Cell Disease

Inclusion Criteria: * Hemoglobin SS, SC, S-β0 Thalassemia, or SO-Arab Sickle Cell Disease * Between the ages of 2 and 25 years (Stage 1: 10-25 years; Stage II: 2-25 years) * Lack a fully matched family donor or fully matched unrelated donor register in the National Marrow Donor Program * Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype * SCD with Severe Phenotype, defined by the following criteria: Neurologic manifestations of sickle disease including cerebral vascular accident (CVA), transient ischemic event (TIA) or abnormal MRI findings suggestive of silent infarct; Two or more episodes of acute chest syndrome (ACS) requiring admission for transfusional or respiratory support including supplemental oxygen within \[two years\] of enrollment in study despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of ACS will also be eligible; History of severe vaso-occlusive (VOC) disease requiring hospitalization and intravenous narcotics on 3 or more occasions per year over the two years prior to enrollment despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of VOC will also be eligible; Other severe phenotype as evidenced by end organ dysfunction related to sickle cell disease. Exclusion Criteria: * Karnofsky or Lansky score \< 60% * Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient has been on chronic transfusion therapy \> 6 months or has a ferritin \> 1000 ng/ml) or AST or ALT \>5 times the upper limit of normal * Severe renal impairment (as evidenced by creatinine clearance of \<50ml/minute glomerular filtration rate (GFR) \< 50% predicted normal) * Cardiac function that demonstrates shortening fraction less than 26% by cardiac echocardiogram or pulmonary hypertension. * Pregnant Female. * Lactating female. * Pulmonary function with baseline O2 saturation \<85% or Diffusing Capacity for Carbon Monoxide (DLCO) on pulmonary function testing (PFT) with a DLCO \<40%.